Description
Subject:- Medicinal chemistry 2
Semester:- 5th sem
Course:- Bachelor of Pharmacy B Pharmacy
Medicinal Chemistry-IIl
ANT-HELMINTICS
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ANTHELMINTICS
• ANTHELMINTICS ARE DRUGS THAT HAVE THE CAPABILITY OF RIDDING THE BODY OF
PARASITIC WORMS OR HELMINTHS
• HELMINTHS THAT INFECT HUMAN HOSTS ARE DIVIDED INTO TWO CATEGORIES, OR
PHYLA:
• A) PLATYHELMINTHES (FLATWORMS)- INCLUDE THE CLASSES CESTODE
(TAPEWORMS) AND TREMATODE (FLUKES OR SCHISTOSOMES)
• B) ASCHELMINTHES OR NEMATODES (ROUNDWORMS)- ROUNDWORM,
HOOKWORM, PINWORM, AND WHIPWORM. THESE WORMS ARE CYLINDRICAL IN
SHAPE, WITH SIGNIFICANT VARIATIONS IN SIZE, PROPORTION, AND STRUCTURE
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ANTHELMINTICS
• NEMATODE INFECTIONS
• ANCYLOSTOMIASIS OR HOOKWORM INFECTION- AMERICAN HOOKWORM (NECATOR
AMERICANUS) AND THE “OLD WORLD” HOOKWORM (ANCYLOSTOMA DOUDENALE).
• ENTEROBIASIS OR PINWORM INFECTION- ENTEROBIUS VERMICULARIS
• ASCARIASIS OR ROUNDWORM INFECTIONS- ASCARIS LUMBRICOIDES
• TRICHURIASIS OR WHIPWORM INFECTIONS- TRICHURIS TRICHIURA
• TRICHINOSIS OR TRICHINA INFECTION- TRICHINELLA SPIRALIS
• FILARIASIS- WUCHERERIA BANCROFTI, BRUGIA MALAYI, AND BRUGIA TIMORI
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ANTHELMINTICS
• CESTODE AND TREMATODE INFECTIONS
• CYSTICERCOSIS OR TAPEWORM INFECTION
• BEEF TAPEWORM (TAENIA SAGINATA)
• PORK TAPEWORM (TAENIA SOLIUM)
• DWARF TAPEWORM (HYMENOLEPIS NANA)
• FISH TAPEWORM (DIPHYLLOBOTHRIUM LATUM)
• SCHISTOSOMIASIS OR BLOOD FLUKES- SCHISTOSOMA HEMATOBIUM,
SCHISTOSOMA MANSONI, AND SCHISTOSOMA JAPONICUM
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DIETHYLCARBAMAZINE CITRATE
• HIGHLY WATER-SOLUBLE CRYSTALLINE COMPOUND THAT HAS SELECTIVE ANTHELMINTIC
ACTIVITY
• IT IS EFFECTIVE AGAINST VARIOUS FORMS OF FILARIASIS, INCLUDING BANCROFT,
ONCHOCERCIASIS, AND LAVIASIS
• IT IS ALSO ACTIVE AGAINST ASCARIASIS
• MECHANIM- NOT CLEARLY KNOWN
• SUGGESTION- INHIBITION OF MICROTUBULE POLYMERIZATION AND DISRUPTION OF
PREFORMED MICROTUBULES
• OR INTERFERENCE WITH ARACHIDONIC ACID METABOLISM
• ADVERSE REACTIONS- ANAPHYLACTIC REACTIONS, INTENSE PRURITUS, AND OCULAR
COMPLICATIONS
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THIABENDAZOLE
• OCCURS AS A WHITE CRYSTALLINE SUBSTANCE THAT IS ONLY SLIGHTLY SOLUBLE IN
WATER BUT IS SOLUBLE IN STRONG MINERAL ACIDS.
• THIABENDAZOLE IS A BASIC COMPOUND WITH A PKA OF 4.7 THAT FORMS
COMPLEXES WITH METAL IONS
• MECHANISM- INHIBITS THE HELMINTH-SPECIFIC ENZYME FUMARATE REDUCTASE
(IMPORTANT ENZYME IN HELMINTHES THAT APPEARS TO BE INVOLVED IN
OXIDATION OF NADH TO NAD FOR ATP PRODUCTION)
• ALSO ARREST NEMATODE CELL DIVISION IN METAPHASE BY INTERFERING WITH
MICROTUBULE ASSEMBLY AND EXHIBIT A HIGH AFFINITY FOR TUBULIN, THE
PRECURSOR PROTEIN FOR MICROTUBULE SYNTHESIS
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THIABENDAZOLE
• HAS BROAD-SPECTRUM ANTHELMINTIC ACTIVITY
• IT IS USED TO TREAT ENTEROBIASIS, STRONGYLOIDIASIS (THREADWORM
INFECTION), ASCARIASIS, UNCINARIASIS (HOOKWORM INFECTION), AND
TRICHURIASIS (WHIPWORM INFECTION)
• ALSO USED TO RELIEVE SYMPTOMS ASSOCIATED WITH CUTANEOUS LARVA
MIGRANS (CREEPING ERUPTION) AND THE INVASIVE PHASE OF TRICHINOSIS.
• WIDELY USED IN VETERINARY PRACTICE TO CONTROL INTESTINAL HELMINTHS IN
LIVESTOCK
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MEBENDAZOLE
• BROAD-SPECTRUM ANTHELMINTIC THAT IS EFFECTIVE AGAINST VARIOUS NEMATODE
INFESTATIONS, INCLUDING WHIPWORM, PINWORM, ROUNDWORM, AND HOOKWORM
• MECHANISM- IRREVERSIBLY BLOCKS GLUCOSE UPTAKE IN SUSCEPTIBLE HELMINTHS,
THEREBY DEPLETING GLYCOGEN STORED IN THE PARASITE
• IT APPARENTLY DOES NOT AFFECT GLUCOSE METABOLISM IN THE HOST. IT ALSO INHIBITS
CELL DIVISION IN NEMATODES
• POORLY ABSORBED BY THE ORAL ROUTE
• ADVERSE REACTIONS ARE UNCOMMON AND USUALLY ABDOMINAL DISCOMFORT
• IT IS TERATOGENIC IN LABORATORY ANIMALS AND SHOULD NOT BE GIVEN DURING
PREGNANCY
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ALBENDAZOLE
• BROAD-SPECTRUM ANTHELMINTIC THAT IS NOT CURRENTLY MARKETED IN NORTH
AMERICA
• WIDELY USED THROUGHOUT THE WORLD FOR THE TREATMENT OF INTESTINAL
NEMATODE INFECTION
• IT IS EFFECTIVE AS A SINGLE-DOSE TREATMENT FOR ASCARIASIS, NEW AND OLD
WORLD HOOKWORM INFECTIONS, AND TRICHURIASIS
• MULTIPLE-DOSE THERAPY WITH ALBENDAZOLE CAN ERADICATE PINWORM,
THREADWORM, CAPILLARIASIS, CLONORCHIASIS, AND HYDATID DISEASE
• EFFECTIVENESS OF ALBENDAZOLE AGAINST TAPEWORMS (CESTODES) IS
GENERALLY MORE VARIABLE AND LESS IMPRESSIVE
• WHITE CRYSTALLINE POWDER THAT IS VIRTUALLY INSOLUBLE IN WATER
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ALBENDAZOLE
• ORAL ABSORPTION OF ALBENDAZOLE IS ENHANCED BY A FATTY MEAL
• DRUG UNDERGOES RAPID AND EXTENSIVE FIRST-PASS METABOLISM TO THE
SULFOXIDE, WHICH IS THE ACTIVE FORM IN PLASMA
• ELIMINATION HALF-LIFE OF THE SULFOXIDE RANGES FROM 10 TO 15 HOURS
• HIGH DOSE CAN RESULT IN ADVERSE EFFECTS SUCH AS BONE MARROW
DEPRESSION, ELEVATION OF HEPATIC ENZYMES, AND ALOPECIA
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NICLOSAMIDE
• OCCURS AS A YELLOWISH WHITE, WATER-INSOLUBLE POWDER
• POTENT TAENIACIDE THAT CAUSES RAPID DISINTEGRATION OF
WORM SEGMENTS AND THE SCOLEX
• PENETRATION OF THE DRUG INTO VARIOUS CESTODES APPEARS TO
BE FACILITATED BY THE DIGESTIVE JUICES OF THE HOST
• NICLOSAMIDE IS WELL TOLERATED FOLLOWING ORAL
ADMINISTRATION, AND LITTLE OR NO SYSTEMIC ABSORPTION OF IT
OCCURS
• A SALINE PURGE 1 TO 2 HOURS AFTER INGESTION OF THE
TAENIACIDE IS RECOMMENDED TO REMOVE THE DAMAGED SCOLEX
AND WORM SEGMENTS- MANDATORY
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OXAMNIQUINE
• ANTISCHISTOSOMAL AGENT THAT IS INDICATED FOR THE TREATMENT OF SCHISTOSOMA
MANSONI (INTESTINAL SCHISTOSOMIASIS) INFECTION
• MECHANISM- SHOWN TO INHIBIT DNA, RNA, AND PROTEIN SYNTHESIS IN SCHISTOSOMES
• 6-HYDROXYMETHYL GROUP IS CRITICAL FOR ACTIVITY;
• METABOLIC ACTIVATION OF PRECURSOR 6-METHYL DERIVATIVES IS CRITICAL
• FREE BASE OCCURS AS A YELLOW CRYSTALLINE SOLID THAT IS SLIGHTLY SOLUBLE IN
WATER BUT SOLUBLE IN DILUTE AQUEOUS MINERAL ACIDS AND SOLUBLE IN MOST
ORGANIC SOLVENTS
• DIZZINESS AND DROWSINESS ARE COMMON, BUT TRANSITORY, SIDE EFFECTS
• SERIOUS REACTIONS, SUCH AS EPILEPTIFORM CONVULSIONS, ARE RARE
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PRAZIQUANTEL
• BROAD-SPECTRUM AGENT THAT IS EFFECTIVE AGAINST VARIOUS TREMATODES
(FLUKES)
• IT HAS BECOME THE AGENT OF CHOICE FOR THE TREATMENT OF INFECTIONS
CAUSED BY SCHISTOSOMES (BLOOD FLUKES)
• EFFECTIVE TREATMENT FOR FASCIOLOPSIASIS (INTESTINAL FLUKE), CLONORCHIASIS
(CHINESE LIVER FLUKE), FASCIOLIASIS (SHEEP LIVER FLUKE), OPISTHORCHOSIS (LIVER
FLUKE), AND PARAGONIMIASIS (LUNG FLUKE)
• MECHANISM- INCREASES CELL MEMBRANE PERMEABILITY OF SUSCEPTIBLE WORMS,
RESULTING IN THE LOSS OF EXTRACELLULAR CALCIUM. MASSIVE CONTRACTIONS
AND ULTIMATE PARALYSIS OF THE FLUKE MUSCULATURE OCCURS, FOLLOWED BY
PHAGOCYTOSIS OF THE PARASITE
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PRAZIQUANTEL
• ORAL ADMINISTRATION, ABOUT 80% OF THE DOSE IS ABSORBED
• DRUG IS RAPIDLY METABOLIZED IN THE LIVER IN THE FIRST-PASS
• WHITE CRYSTALLINE SOLID THAT IS INSOLUBLE IN WATER
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IVERMECTIN
• IS A MIXTURE OF 22,23-DIHYDRO DERIVATIVES OF AVERMECTINS B1A AND B1B PREPARED BY
CATALYTIC HYDROGENATION
• AVERMECTINS ARE MEMBERS OF A FAMILY OF STRUCTURALLY COMPLEX ANTIBIOTICS
PRODUCED BY FERMENTATION WITH A STRAIN OF STREPTOMYCES AVERMITILIS
• IVERMECTIN IS ACTIVE IN LOW DOSAGE AGAINST A WIDE VARIETY OF NEMATODES AND
ARTHROPODS THAT PARASITIZE ANIMALS
• STRUCTURE- PENTACYCLIC 16-MEMBERED–RING AGLYCONES GLYCOSIDICALLY LINKED AT
THE 3-POSITION TO A DISACCHARIDE THAT COMPRISES TWO OLEANDROSE SUGAR
RESIDUES
• SIDE CHAIN AT THE 25-POSITION OF THE AGLYCONE IS SEC-BUTYL IN AVERMECTIN B1A,
WHEREAS IN AVERMECTIN B1B, IT IS ISOPROPYL
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AVERMECTINS B1A (-C2H5) AND B1B (-CH3)
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IVERMECTIN
• IVERMECTIN CONTAINS AT LEAST 80% OF 22,23-DIHYDROAVERMECTIN B1A AND
NO MORE THAN 20% 22,23-DIHYDROAVERMECTIN B1B
• WIDESPREAD USE IN VETERINARY PRACTICE IN THE UNITED STATES AND MANY
COUNTRIES THROUGHOUT THE WORLD FOR THE CONTROL OF ENDOPARASITES
AND ECTOPARASITES IN DOMESTIC ANIMALS
• IT HAS BEEN FOUND EFFECTIVE FOR THE TREATMENT OF ONCHOCERCIASIS (“RIVER
BLINDNESS”) IN HUMANS, AN IMPORTANT DISEASE CAUSED BY THE ROUNDWORM
ONCOCERCA VOLVULUS
• MECHANISM- IT BLOCKS INTERNEURON–MOTOR NEURON TRANSMISSION IN
NEMATODES BY STIMULATING THE RELEASE OF THE INHIBITORY NEUROTRANSMITTER
GABA
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DIETHYLCARBAMAZINE CITRATE- SYNTHESIS
N, N-diethyl-4-methyl-1-piperazin 1-methylpiperazine
Carbonyl chloride
Citric acid
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Nitration
MEBENDAZOLE- SYNTHESIS Reduction
4-chlorobenzophenone 3,4-diaminobenzophenone
methyl chloroformate
S-methylthiourea N-methoxycarbonyl-S-methylthiourea
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THANK YOU
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